The octanoylated energy regulating hormone ghrelin: An expanded view of ghrelin’s biological interactions and avenues for controlling ghrelin signaling

Abstract

Ghrelin is a small peptide hormone that requires a unique post-translational modification, serine octanoylation, to bind and activate the GHS-R1a receptor. Initially demonstrated to stimulate hunger and appetite, ghrelin-dependent signaling is implicated in a variety of neurological and physiological processes influencing diseases such as diabetes, obesity, and Prader-Willi syndrome. In addition to its cognate receptor, recent studies have revealed ghrelin interacts with a range of binding partners within the bloodstream. Defining the scope of ghrelin’s interactions within the body, understanding how these interactions work in concert to modulate ghrelin signaling, and developing molecular tools for controlling ghrelin signaling are essential for exploiting ghrelin for therapeutic effect. In this review, we discuss recent findings regarding the biological effects of ghrelin signaling, outline binding partners that control ghrelin trafficking and stability in circulation, and summarize the current landscape of inhibitors targeting ghrelin octanoylation.

Keywords:

• Ghrelin
• ghrelin O-acyltransferase
• protein acylation
• ghrelin O-acyltransferase inhibitors

Acknowledgements

We thank members of the Hougland research group for discussions and helpful comments.

Disclosure statement

JLH has patent interests in the use of multiple compounds reported herein to target ghrelin signaling and associated health conditions. The other authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.

Additional information

Funding

We gratefully acknowledge funding support from the American Diabetes Association to JLH [1-16-JDF-042].